Isolated aplastic anemia, also known as bone marrow failure is a serious disease characterized by intense decrease or absence of erythrocytes, granulocytes and megakaryocytes of the bone marrow, accompanied by the corresponding pancytopenia. It can occur at any age but is most common in young adults and the elderly. In severe cases up to 80% of affected individuals die within 18 to 24 months and in some quick ways even before three months. The causes of death are often infections and bleeding.

This process is due to mutations in the TERC gene, located on the long arm of chromosome 3 (3q26) and TERT, located on the short arm of chromosome 5 (5p15.33). These genes encode components of an enzyme called telomerase. Telomerase maintains telomeres, which are composed of repeated DNA segments found in the ends of chromosomes. Telomeres protect the chromosomes so that no sticking together abnormally or degrade. In most cells, the telomeres become progressively shorter as the cell divides. After a certain number of cell divisions, the telomeres become so short that cause the cell to stop dividing or apoptosis occurs. Telomerase counteracts the shortening of telomeres by adding small DNA repeated segments to the ends of chromosomes each time the cell divides. In most types of cells, telomerase is active at very low concentrations or is virtually undetectable. However, telomerase is active in the cells that the cells in the bone marrow and cells of the developing fetus rapidly dividing, such as the cells lining the lungs and gastrointestinal tract. Telomerase allows these cells to divide many times without being damaged or apoptosis to occur. Telomerase is also abnormally active in cancer cells, which grow and divide without control or order.

Telomerase enzyme consists of two main components which act together. One component, known as hTR, is encoded from the TERC gene. The hTR component is an RNA molecule that provides a template for creating repeated DNA sequence that telomerase adds to the ends of chromosomes. The other major component of telomerase, known as hTERT, is encoded from TERT gene. HTERT function is to add the new DNA segment to the ends of chromosomes.

Mutations in TERC and TERT genes lead to dysfunction of telomerase, deterioration in telomere maintenance, and reducing telomere length. It is believed that the isolated aplastic anemia due to mutations in the gene TERC actually may represent late - onset form of dyskeratosis congenita in which the physical characteristics such as nail dystrophy are mild and may not be detectable.

Tests in IVAMI: in IVAMI perform detection of mutations associated with aplastic anemia isolated by PCR amplification the complete exons of TERC and TERT genes, respectively, and subsequent sequencing.

Samples recommended:EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).